Work is proposed on three projects involving interferon. First, we wish to determine whether reduction of the stability (that is, the half-life) of viral messenger RNAs plays a role in the mechanism of antiviral action of interferon. Specifically, we wish to measure the half-life of vaccinia virus, VSV and EMC virus messenger RNAs in normal and interferon-treated cells. Second, we will continue our studies to clone a mouse interferon gene. Once such a gene has been cloned, the mouse interferon DNA will be used to isolate pure messenger RNA of the homologous human interferon gene, which will then be cloned in vectors and under conditions that are most likely to lead to its complete expression. Finally, we propose a series of studies to isolate human cells capable of producing interferon constitutively. Cells will be mutagenized, and a variety of human cell lines will be surveyed for their ability to yield constitutive interferon producers by selecting those able to resist infection with virus.